BCL2 antibodies targeted at different epitopes detect varying levels of protein expression and correlate with frequent gene amplification in diffuse large B-cell lymphoma.
BCL2 antibodies targeted at different epitopes detect varying levels of protein expression and correlate with frequent gene amplification in diffuse large B-cell lymphoma.
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DOI：
10.1016/j.humpath.2014.06.005
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发表时间：
2014-10
期刊：
影响因子：
3.3
通讯作者：
Rimsza, Lisa M.
中科院分区：
文献类型：
--
作者：
Kendrick, Samantha L.;Redd, Lucas;Muranyi, Andrea;Henricksen, Leigh A.;Stanislaw, Stacey;Smith, Lynette M.;Perry, Anamarija M.;Fu, Kai;Weisenburger, Dennis D.;Rosenwald, Andreas;Ott, German;Gascoyne, Randy D.;Jaffe, Elaine S.;Campo, Elias;Delabie, Jan;Braziel, Rita M.;Cook, James R.;Tubbs, Raymond R.;Staudt, Louis M.;Chan, Wing Chung;Steidl, Christian;Grogan, Thomas M.;Rimsza, Lisa M.
关键词：
具有侵袭性、BCL 2蛋白阳性（+）弥漫性大B细胞淋巴瘤（DLBCL）的患者通常经历标准治疗难治的快速疾病进展。然而，使用标准单克隆小鼠124抗体进行BCL 2的假阴性染色可能会阻碍这些高风险DLBCL患者的识别。在此，我们比较了两种替代兔单克隆抗体（E17和SP 66）的124克隆在福尔马林固定，石蜡包埋DLBCL组织中的BCL 2染色。总体而言，在两个独立的DLBCL组群中，E17和SP 66比124更频繁地检测到BCL 2表达。在MYC表达的背景下，用SP 66鉴定为BCL 2（+）的病例证明与更差的OS最强的相关性。124克隆在大多数易位（+）、扩增（+）和活化的B细胞DLBCL病例中未能检测到BCL 2表达，其中预期高水平的BCL 2蛋白。使用双重原位杂交（Dual ISH）作为检测BCL 2易位和扩增的新工具，我们观察到与先前报道的荧光ISH易位相似的结果，但扩增频率更高，表明BCL 2扩增可能在DLBCL中被低估。在差异病例中，BCL 2在T69和/或S70的磷酸化比一致病例中更常见，并且可能导致124例假阴性，除了先前在表位区域内的相关突变。准确检测BCL 2表达对于DLBCL的预后和治疗非常重要，特别是使用新的抗BCL 2疗法。
Patients with aggressive, BCL2 protein-positive (+) diffuse large B-cell lymphoma (DLBCL) often experience rapid disease progression that is refractory to standard therapy. However, there is potential for false-negative staining of BCL2 using the standard monoclonal mouse 124 antibody that hinders the identification of these high-risk DLBCL patients. Herein, we compare two alternative rabbit monoclonal antibodies (E17 and SP66) to the 124 clone in staining for BCL2 in formalin-fixed, paraffin-embedded DLBCL tissues. Overall, in two independent DLBCL cohorts E17 and SP66 detected BCL2 expression more frequently than 124. In the context of MYC expression, cases identified as BCL2 (+) with SP66 demonstrated the strongest correlation with worse OS. The 124 clone failed to detect BCL2 expression in the majority of translocation (+), amplification (+), and activated B-cell DLBCL cases in which high levels of BCL2 protein are expected. Using dual in-situ hybridization (Dual ISH) as a new tool to detect BCL2 translocation and amplification, we observed similar results as previously reported for fluorescence ISH for translocation but a higher amplification frequency, indicating that BCL2 amplification may be under-reported in DLBCL. Among the discrepant cases, phosphorylation of BCL2 at T69 and/or S70 was more common than in the concordant cases and may contribute to the 124 false-negatives, in addition to previously associated mutations within the epitope region. The accurate detection of BCL2 expression is important in the prognosis and treatment of DLBCL particularly with new anti-BCL2 therapies.
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影响因子：
10.1
作者：
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通讯作者：
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影响因子：
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作者：
Meyer, Paul N.;Fu, Kai;Weisenburger, Dennis D.
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